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https://www.readbyqxmd.com/read/27913437/surface-expression-of-tgf%C3%AE-docking-receptor-garp-promotes-oncogenesis-and-immune-tolerance-in-breast-cancer
#1
Alessandra Metelli, Bill X Wu, Caroline W Fugle, Saleh Rachidi, Shaoli Sun, Yongliang Zhang, Jennifer Wu, Stephen Tomlinson, Philip H Howe, Yi Yang, Elizabeth Garrett-Mayer, Bei Liu, Zihai Li
GARP encoded by the Lrrc32 gene is the cell surface docking receptor for latent TGFβ, which is expressed naturally by platelets and regulatory T cells (Treg). Although Lrrc32 is amplified frequently in breast cancer, the expression and relevant functions of GARP in cancer have not been explored. Here, we report that GARP exerts oncogenic effects, promoting immune tolerance by enriching and activating latent TGFβ in the tumor microenvironment. We found that human breast, lung, and colon cancers expressed GARP aberrantly...
October 20, 2016: Cancer Research
https://www.readbyqxmd.com/read/27884290/atopic-dermatitis-according-to-garp-new-mechanistic-insights-in-disease-pathogenesis
#2
Janna Nousbeck, Alan D Irvine
In complex disease such as atopic dermatitis, the journey from identification of strong risk loci to profound functional and mechanistic insights can take several years. Here, Manz et al. have elegantly deciphered the mechanistic pathways in the well-established 11q13.5 atopic dermatitis risk locus. Their genetic and functional insights emphasize a role for T regulatory cells in atopic dermatitis pathogenesis.
December 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27777305/expansion-of-lysine-rich-repeats-in-plasmodium-proteins-generates-novel-localisation-sequences-that-target-the-periphery-of-the-host-erythrocyte
#3
Heledd M Davies, Konstantinos Thalassinos, Andrew R Osborne
Repetitive low-complexity sequences, mostly assumed to have no function, are common in proteins that are exported by the malaria parasite into its host erythrocyte. We identify a group of exported proteins containing short lysine-rich tandemly repeated sequences that are sufficient to localise to the erythrocyte periphery where key virulence-related modifications to the plasma membrane and the underlying cytoskeleton are known to occur. Efficiency of targeting is dependent on repeat number, indicating that novel targeting modules could evolve by expansion of short lysine-rich sequences...
October 24, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27757121/golden-2-like-transcription-factors-of-plants
#4
Min Chen, Meiling Ji, Binbin Wen, Li Liu, Shaoxuan Li, Xiude Chen, Dongsheng Gao, Ling Li
Golden2-like (GLK) transcription factors are members of the GARP family of Myb transcription factors with an established relationship to chloroplast development in the plant kingdom. In the last century, Golden2 was proposed as a second golden producing factor and identified as controlling cellular differentiation in maize leaves. Then, GLKs were also found to play roles in disease defense and their function is conserved in regulating chloroplast development. Recently, research on GLKs has rapidly increased and shown that GLKs control chloroplast development in green and non-green tissues...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27581988/vaccinia-virus-uses-retromer-independent-cellular-retrograde-transport-pathways-to-facilitate-the-wrapping-of-intracellular-mature-virions-during-viral-morphogenesis
#5
Kate Harrison, Ismar R Haga, Tali Pechenick Jowers, Seema Jasim, Jean-Christophe Cintrat, Daniel Gillet, Thomas Schmitt-John, Paul Digard, Philippa M Beard
: Poxviruses such as Vaccinia virus (VACV) undertake a complex cytoplasmic replication cycle which involves morphogenesis through four distinct virion forms, and includes a crucial "wrapping" step whereby intracellular mature virions (IMVs) are wrapped in two additional membranes to form intracellular enveloped virions (IEVs). To determine if cellular retrograde transport pathways were required for this wrapping step we examined VACV morphogenesis in cells with reduced expression of the tetrameric tethering factor complex GARP (Golgi-associated retrograde pathway complex), a central component of retrograde transport...
August 31, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27462928/autophagy-in-saccharomyces-cerevisiae-requires-the-monomeric-gtp-binding-proteins-arl1-and-ypt6
#6
Shu Yang, Anne G Rosenwald
Macroautophagy/autophagy is a cellular degradation process that sequesters organelles or proteins into a double-membrane structure called the phagophore; this transient compartment matures into an autophagosome, which then fuses with the lysosome or vacuole to allow hydrolysis of the cargo. Factors that control membrane traffic are also essential for each step of autophagy. Here we demonstrate that 2 monomeric GTP-binding proteins in Saccharomyces cerevisiae, Arl1 and Ypt6, which belong to the Arf/Arl/Sar protein family and the Rab family, respectively, and control endosome-trans-Golgi traffic, are also necessary for starvation-induced autophagy under high temperature stress...
October 2, 2016: Autophagy
https://www.readbyqxmd.com/read/27458219/divergent-transcriptional-responses-to-physiological-and-xenobiotic-stress-in-giardia-duodenalis
#7
Brendan R E Ansell, Malcolm J McConville, Louise Baker, Pasi K Korhonen, Samantha J Emery, Staffan G Svärd, Robin B Gasser, Aaron R Jex
Understanding how parasites respond to stress can help to identify essential biological processes. Giardia duodenalis is a parasitic protist that infects the human gastrointestinal tract and causes 200 to 300 million cases of diarrhea annually. Metronidazole, a major antigiardial drug, is thought to cause oxidative damage within the infective trophozoite form. However, treatment efficacy is suboptimal, due partly to metronidazole-resistant infections. To elucidate conserved and stress-specific responses, we calibrated sublethal metronidazole, hydrogen peroxide, and thermal stresses to exert approximately equal pressure on trophozoite growth and compared transcriptional responses after 24 h of exposure...
October 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27448748/targeted-resequencing-and-functional-testing-identifies-low-frequency-missense-variants-in-the-gene-encoding-garp-as-significant-contributors-to-atopic-dermatitis-risk
#8
Judith Manz, Elke Rodríguez, Abdou ElSharawy, Eva-Maria Oesau, Britt-Sabina Petersen, Hansjörg Baurecht, Gabriele Mayr, Susanne Weber, Jürgen Harder, Eva Reischl, Agatha Schwarz, Natalija Novak, Andre Franke, Stephan Weidinger
Gene-mapping studies have consistently identified a susceptibility locus for atopic dermatitis and other inflammatory diseases on chromosome band 11q13.5, with the strongest association observed for a common variant located in an intergenic region between the two annotated genes C11orf30 and LRRC32. Using a targeted resequencing approach we identified low-frequency and rare missense mutations within the LRRC32 gene encoding the protein GARP, a receptor on activated regulatory T cells that binds latent transforming growth factor-β...
July 21, 2016: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/27440922/tssc1-is-novel-component-of-the-endosomal-retrieval-machinery
#9
David C Gershlick, Christina Schindler, Yu Chen, Juan S Bonifacino
Endosomes function as a hub for multiple protein-sorting events, including retrograde transport to the trans-Golgi network (TGN) and recycling to the plasma membrane. These processes are mediated by tubular-vesicular carriers that bud from early endosomes and fuse with a corresponding acceptor compartment. Two tethering complexes named GARP (composed of ANG2, VPS52, VPS53, and VPS54 subunits) and EARP (composed of ANG2, VPS52, VPS53, and Syndetin subunits) were previously shown to participate in SNARE-dependent fusion of endosome-derived carriers with the TGN and recycling endosomes, respectively...
September 15, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/27428774/catchr-hops-and-corvet-tethering-complexes-share-a-similar-architecture
#10
Hui-Ting Chou, Danijela Dukovski, Melissa G Chambers, Karin M Reinisch, Thomas Walz
We show here that the Saccharomyces cerevisiae GARP complex and the Cog1-4 subcomplex of the COG complex, both members of the complexes associated with tethering containing helical rods (CATCHR) family of multisubunit tethering complexes, share the same subunit organization. We also show that HOPS, a tethering complex acting in the endolysosomal pathway, shares a similar architecture, thus suggesting that multisubunit tethering complexes use related structural frameworks.
August 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27415620/uncontrolled-il-17-production-by-intraepithelial-lymphocytes-in-a-case-of-non-ipex-autoimmune-enteropathy
#11
Moira Paroni, Andrea Magarotto, Silvia Tartari, Giulia Nizzoli, Paola Larghi, Giulia Ercoli, Umberto Gianelli, Massimiliano Pagani, Luca Elli, Sergio Abrignani, Dario Conte, Jens Geginat, Flavio Caprioli
OBJECTIVES: To provide a functional and phenotypic characterization of immune cells infiltrating small intestinal mucosa during non-IPEX autoimmune enteropathy (AIE), as to gain insights on the pathogenesis of this clinical condition. METHODS: Duodenal biopsies from a patient with AIE at baseline and following drug-induced remission were analyzed by immunohistochemistry, immunofluorescence, and flow cytometry, and results were compared with those obtained from patients with active celiac disease, ileal Crohn's disease and healthy controls...
2016: Clinical and Translational Gastroenterology
https://www.readbyqxmd.com/read/27366089/decreased-foxp3-and-garp-tregs-to-neoadjuvant-chemotherapy-associated-with-favorable-prognosis-in-advanced-gastric-cancer
#12
Kai Li, Fuchao Chen, Huijuan Xie
Neoadjuvant chemotherapy (NACT) has been an increasingly used therapeutic strategy to improve the outcome of advanced gastric cancer (GC) over the past few decades. Lymphocytic infiltration has been reported to be associated with response to NACT, but the immune cell subpopulation and its prognosis contributing to response in GC have not been clarified yet. In the current study, the tumor infiltration of FOXP3+ and GARP+ regulatory T-cells (Tregs, marked by FOXP3 and GARP) response to NACT in advanced GC and their correlation with prognosis were evaluated...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27280981/redefining-the-australian-anthrax-belt-modeling-the-ecological-niche-and-predicting-the-geographic-distribution-of-bacillus-anthracis
#13
Alassane S Barro, Mark Fegan, Barbara Moloney, Kelly Porter, Janine Muller, Simone Warner, Jason K Blackburn
The ecology and distribution of B. anthracis in Australia is not well understood, despite the continued occurrence of anthrax outbreaks in the eastern states of the country. Efforts to estimate the spatial extent of the risk of disease have been limited to a qualitative definition of an anthrax belt extending from southeast Queensland through the centre of New South Wales and into northern Victoria. This definition of the anthrax belt does not consider the role of environmental conditions in the distribution of B...
June 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27248166/a-key-role-of-garp-in-the-immune-suppressive-tumor-microenvironment
#14
Susanne A Hahn, Annemarie Neuhoff, Jenny Landsberg, Jonathan Schupp, Daniela Eberts, Petra Leukel, Matthias Bros, Martin Weilbaecher, Detlef Schuppan, Stephan Grabbe, Thomas Tueting, Volker Lennerz, Clemens Sommer, Helmut Jonuleit, Andrea Tuettenberg
In melanoma patients, one of the main reasons for tumor immune escape and therapy failure is the immunosuppressive tumor microenvironment. Herein, suppressive immune cells and inhibitory factors secreted by the tumor itself play a central role.In the present study we show that the Treg activation marker GARP (glycoprotein A repetitions predominant), known to induce peripheral tolerance in a TGF-β dependent way, is also expressed on human primary melanoma. Interestingly, membrane bound GARP is shed from the surface of both, activated Treg and melanoma cells, and, in its soluble form (sGARP), not only induces peripheral Treg but also a tumor associated (M2) macrophage phenotype...
May 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/27244900/retinoic-acid-treated-human-dendritic-cells-induce-t-regulatory-cells-via-the-expression-of-cd141-and-garp-which-is-impaired-with-age
#15
Sudhanshu Agrawal, Sreerupa Ganguly, Alexander Tran, Padmaja Sundaram, Anshu Agrawal
Aged subjects display increased susceptibility to mucosal diseases. Retinoic Acid (RA) plays a major role in inducing tolerance in the mucosa. RA acts on Dendritic cells (DCs) to induce mucosal tolerance. Here we compared the response of DCs from aged and young individuals to RA with a view to understand the role of DCs in age-associated increased susceptibility to mucosal diseases. Our investigations revealed that compared to young DCs, RA stimulated DCs from aged subjects are defective in inducing IL-10 and T regulatory cells...
June 2016: Aging
https://www.readbyqxmd.com/read/27243003/membrane-tethering-complexes-in-the-endosomal-system
#16
REVIEW
Anne Spang
Vesicles that are generated by endocytic events at the plasma membrane are destined to early endosomes. A prerequisite for proper fusion is the tethering of two membrane entities. Tethering of vesicles to early endosomes is mediated by the class C core vacuole/endosome tethering (CORVET) complex, while fusion of late endosomes with lysosomes depends on the homotypic fusion and vacuole protein sorting (HOPS) complex. Recycling through the trans-Golgi network (TGN) and to the plasma membrane is facilitated by the Golgi associated retrograde protein (GARP) and endosome-associated recycling protein (EARP) complexes, respectively...
2016: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/27141368/targeting-immunosuppression-by-tregs-with-monoclonal-antibodies-against-garp
#17
Stéphanie Liénart, Julie Stockis, Olivier Dedobbeleer, Sophie Lucas
Reducing Treg function in cancer patients should augment antitumor immune responses. We recently uncovered a mechanism of immunosuppression by human Tregs that implies transmembrane protein GARP and production of active TGF-ß1. We obtained monoclonal antibodies that block this process and could thus serve as a novel approach for cancer immunotherapy.
March 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27134727/associations-between-joint-effusion-in-the-knee-and-gene-expression-levels-in-the-circulation-a-meta-analysis
#18
Marjolein J Peters, Yolande F M Ramos, Wouter den Hollander, Dieuwke Schiphof, Albert Hofman, André G Uitterlinden, Edwin H G Oei, P Eline Slagboom, Margreet Kloppenburg, Johan L Bloem, Sita M A Bierma-Zeinstra, Ingrid Meulenbelt, Joyce B J van Meurs
OBJECTIVE: To identify molecular biomarkers for early knee osteoarthritis (OA), we examined whether joint effusion in the knee associated with different gene expression levels in the circulation. MATERIALS AND METHODS: Joint effusion grades measured with magnetic resonance (MR) imaging and gene expression levels in blood were determined in women of the Rotterdam Study (N=135) and GARP (N=98). Associations were examined using linear regression analyses, adjusted for age, fasting status, RNA quality, technical batch effects, blood cell counts, and BMI...
2016: F1000Research
https://www.readbyqxmd.com/read/27095576/garp-a-surface-molecule-of-regulatory-t-cells-that-is-involved-in-the-regulatory-function-and-tgf-%C3%AE-releasing
#19
REVIEW
Liping Sun, Hao Jin, Hui Li
There are many molecules that define regulatory T cells (Tregs) phenotypically and functionally. Glycoprotein A repetitions predominant (GARP) is a transmembrane protein containing leucine rich repeats. Recently, GARP is found to express highly on the surface of activated Tregs. The combination of GARP and other surface molecules isolates Tregs with higher purity. Besides, GARP is a cell surface molecule of Tregs that maintains their regulatory function and homeosatsis. GARP has also been proved to promote the activation and secretion of transforming growth factor β (TGF-β)...
July 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/27072698/clients-and-oncogenic-roles-of-molecular-chaperone-gp96-grp94
#20
REVIEW
Ephraim A Ansa-Addo, Jessica Thaxton, Feng Hong, Bill X Wu, Yongliang Zhang, Caroline W Fugle, Alessandra Metelli, Brian Riesenberg, Katelyn Williams, Daniel T Gewirth, Gabriela Chiosis, Bei Liu, Zihai Li
As an endoplasmic reticulum heat shock protein (HSP) 90 paralogue, glycoprotein (gp) 96 possesses immunological properties by chaperoning antigenic peptides for activation of T cells. Genetic studies in the last decade have unveiled that gp96 is also an essential master chaperone for multiple receptors and secreting proteins including Toll-like receptors (TLRs), integrins, the Wnt coreceptor, Low Density Lipoprotein Receptor-Related Protein 6 (LRP6), the latent TGFβ docking receptor, Glycoprotein A Repetitions Predominant (GARP), Glycoprotein (GP) Ib and insulin-like growth factors (IGF)...
2016: Current Topics in Medicinal Chemistry
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